- Remarkably Efficient Iridium Catalysts for Directed C(sp2)-H and C(sp3)-H Borylation of Diverse Classes of Substrates
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Here we describe the discovery of a new class of C-H borylation catalysts and their use for regioselective C-H borylation of aromatic, heteroaromatic, and aliphatic systems. The new catalysts have Ir-C(thienyl) or Ir-C(furyl) anionic ligands instead of the diamine-type neutral chelating ligands used in the standard C-H borylation conditions. It is reported that the employment of these newly discovered catalysts show excellent reactivity and ortho-selectivity for diverse classes of aromatic substrates with high isolated yields. Moreover, the catalysts proved to be efficient for a wide number of aliphatic substrates for selective C(sp3)-H bond borylations. Heterocyclic molecules are selectively borylated using the inherently elevated reactivity of the C-H bonds. A number of late-stage C-H functionalization have been described using the same catalysts. Furthermore, we show that one of the catalysts could be used even in open air for the C(sp2)-H and C(sp3)-H borylations enabling the method more general. Preliminary mechanistic studies suggest that the active catalytic intermediate is the Ir(bis)boryl complex, and the attached ligand acts as bidentate ligand. Collectively, this study underlines the discovery of new class of C-H borylation catalysts that should find wide application in the context of C-H functionalization chemistry.
- Chattopadhyay, Buddhadeb,Hassan, Mirja Md Mahamudul,Hoque, Md Emdadul
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supporting information
p. 5022 - 5037
(2021/05/04)
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- Palladium-Catalyzed Chlorocarbonylation of Aryl (Pseudo)Halides Through In Situ Generation of Carbon Monoxide
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An efficient palladium-catalyzed chlorocarbonylation of aryl (pseudo)halides that gives access to a wide range of carboxylic acid derivatives has been developed. The use of butyryl chloride as a combined CO and Cl source eludes the need for toxic, gaseous carbon monoxide, thus facilitating the synthesis of high-value products from readily available aryl (pseudo)halides. The combination of palladium(0), Xantphos, and an amine base is essential to promote this broadly applicable catalytic reaction. Overall, this reaction provides access to a great variety of carbonyl-containing products through in situ transformation of the generated aroyl chloride. Combined experimental and computational studies support a reaction mechanism involving in situ generation of CO.
- Bismuto, Alessandro,Boehm, Philip,Morandi, Bill,Roediger, Sven
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supporting information
p. 17887 - 17896
(2020/08/19)
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- Formamide catalyzed activation of carboxylic acids-versatile and cost-efficient amidation and esterification
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A novel, broadly applicable method for amide C-N and ester C-O bond formation is presented based on formylpyrrolidine (FPyr) as a Lewis base catalyst. Herein, trichlorotriazine (TCT), which is the most cost-efficient reagent for OH-group activation, was employed in amounts of ≤40 mol% with respect to the starting material (100 mol%). The new approach is distinguished by excellent cost-efficiency, waste-balance (E-factor down to 3) and scalability (up to >80 g). Moreover, high levels of functional group compatibility, which includes acid-labile acetals and silyl ethers, are demonstrated and even peptide C-N bonds can be formed. In comparison to reported amidation procedures using TCT, yields are considerably improved (for instance from 26 to 91%) and esterification is facilitated for the first time in synthetically useful yields. These significant enhancements are rationalized by activation by means of acid chlorides instead of less electrophilic acid anhydride intermediates.
- Huy, Peter H.,Mbouhom, Christelle
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p. 7399 - 7406
(2019/08/20)
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- Functional Group Transposition: A Palladium-Catalyzed Metathesis of Ar-X σ-Bonds and Acid Chloride Synthesis
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We describe the development of a new method to use palladium catalysis to form functionalized aromatics: via the metathesis of covalent σ-bonds between Ar-X fragments. This transformation demonstrates the dynamic nature of palladium-based oxidative addition/reductive elimination and offers a straightforward approach to incorporate reactive functional groups into aryl halides through exchange reactions. The reaction has been exploited to assemble acid chlorides without the use of high energy halogenating or toxic reagents and, instead, via the metathesis of aryl iodides with other acid chlorides.
- De La Higuera Macias, Maximiliano,Arndtsen, Bruce A.
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supporting information
p. 10140 - 10144
(2018/08/23)
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- Method of co-producing methyl benzoic acid, methylbenzoyl chloride and phthaloyl dichloride
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The invention discloses a method of co-producing methyl benzoic acid, methylbenzoyl chloride and phthaloyl dichloride. The method comprises the following steps: (1) continuously introducing xylene, acatalyst and oxygen-containing gas into an oxidizing reactor to react to obtain an oxidized reaction solution; (2) rectifying and separating the oxidized reaction solution to obtain a low-boiling-point component and an initial evaporative tower bottom; (3) rectifying the initial evaporative tower bottom to obtain a methyl benzoic acid product and a tower bottom; (4) carrying out an acylating chlorination reaction on the tower bottom and an acylating chlorination reagent to obtain an acyl chloride reaction solution; and (5) rectifying and separating the acyl chloride reaction solution to separately obtain methylbenzoyl chloride and phthaloyl dichloride products. The method provided by the invention has the advantages of being simple in process, small in equipment investment, green and environment-friendly and good in comprehensive economical benefit.
- -
-
Paragraph 18-24; 27; 28
(2018/06/16)
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- A O-between the - trifluoromethyl benzoic acid to synthetic method (by machine translation)
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The present invention provides a O-between the - trifluoromethyl benzoic acid to the synthesis method, the method comprises the following steps: (1) between adjacent to methyl benzoic acid acylated preparation between neighbour methyl benzoyl chloride; (2) between the adjacent methyl benzoyl chloride to chlorine light between neighbour trichloromethyl benzoyl chloride is obtained; (3) adjacent to the trichloromethyl benzoyl chloride fluoride obtained between between neighbour trifluoromethyl methyl benzoyle fluoride; (4) adjacent to the trifluoromethyl benzoyle fluoride hydrolysis between the final product is obtained between neighbour trifluoromethyl methyl benzoic acid. The method of the invention cheap raw material, the product yield is high, the process is simple, is favorable for industrial production. (by machine translation)
- -
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Paragraph 0028
(2017/12/29)
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- Synthesis method of o-trifluoromethyl methyl benzoate, m-trifluoromethyl methyl benzoate and p-trifluoromethyl methyl benzoate
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The invention provides a synthesis method of o-trifluoromethyl methyl benzoate, m-trifluoromethyl methyl benzoate and p-trifluoromethyl methyl benzoate. The synthesis method comprises the following steps: taking methyl benzoic acid as a raw material, carrying out acylating chlorination to obtain methylbenzoyl chloride, carrying out side-chain chlorination to obtain trichloromethyl benzoyl chloride, carrying out fluorination substitution to obtain trifluoromethyl benzoyl fluoride, and carrying out esterification to obtain a final product which is trifluoromethyl methyl benzoate. The synthesis method can be used for producing the o-trifluoromethyl methyl benzoate, the m-trifluoromethyl methyl benzoate and the p-trifluoromethyl methyl benzoate, is easily available in raw material, mild in reaction mechanism, high in reaction yield, few in reaction by-products, low in yield of three wastes and easy in treatment of three wastes, and is suitable for industrial production.
- -
-
Paragraph 0016
(2018/03/01)
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- C-F bond cleavage enabled redox-neutral [4+1] annulation via C-H bond activation
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Using α,α-difluoromethylene alkyne as a nontraditional one-carbon reaction partner, a synthetically novel method for the construction of isoindolin-1-one derivatives via Rh(III)-catalyzed [4+1] annulation reaction is reported. The 2-fold C-F bond cleavage not only enables the generation of desired product under an overall oxidant-free condition but also results in a net migration of carbon-carbon triple bond. In addition, the present reaction protocol exhibits a tolerance of a wide spectrum of functional groups due to the mild reaction conditions employed.
- Wang, Cheng-Qiang,Ye, Lu,Feng, Chao,Loh, Teck-Peng
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supporting information
p. 1762 - 1765
(2017/02/15)
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- Design, synthesis and biological evaluation of aminobenzyloxyarylamide derivatives as selective κ opioid receptor antagonists
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Opioid receptors play an important role in both behavioral and mood functions. Based on the structural modification of LY2456302, a series of aminobenzyloxyarylamide derivatives were designed and synthesized as κ opioid receptor antagonists. The κ opioid receptor binding ability of these compounds were evaluated with opioid receptors binding assays. Compounds 1a-d showed high affinity for κ opioid receptor. Especially for compound 1c, exhibited a significant Kivalue of 15.7?nM for κ opioid receptor binding and a higher selectivity over μ and δ opioid receptors compared to (±)LY2456302. In addition, compound 1c also showed potent κ antagonist activity with κ IC50?=?9.32?nM in [35S]GTP-γ-S functional assay. The potential use of the representative compounds as antidepressants was also investigated. The most potent compound 1c not only exhibited potent antidepressant activity in the mice forced swimming test, but also displayed the effect of anti-anxiety in the elevated plus-maze test.
- Wang, Junwei,Song, Qiao,Xu, Anhua,Bao, Yu,Xu, Yungen,Zhu, Qihua
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- Iron-Catalyzed C?H Alkynylation through Triazole Assistance: Expedient Access to Bioactive Heterocycles
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Triazole assistance enabled the first iron-catalyzed C?H alkynylation of arenes, heteroarenes, and alkenes. The modular TAM directing group set the stage for a sequential C?H alkynylation/annulation strategy with ample scope, enabling the iron-catalyzed assembly of isoquinolones, pyridones, pyrrolones, and isoindolinones with high levels of chemo-, site-, and regioselectivity.
- Cera, Gianpiero,Haven, Tobias,Ackermann, Lutz
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supporting information
p. 3577 - 3582
(2017/03/20)
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- Metal-free oxidative self-coupling of aldehydes or alcohols to symmetric carboxylic anhydrides
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A metal-free synthesis of symmetrical anhydrides has been developed starting from aldehydes, both aliphatic and aromatic or primary benzylic alcohols. The reaction occurs at room temperature and makes use of trichloroisocyanuric acid (TCCA) as an oxidant providing the desired carboxylic anhydrides in satisfactory yields.
- Gaspa, Silvia,Porcheddu, Andrea,De Luca, Lidia
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supporting information
p. 2533 - 2536
(2017/06/13)
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- Anhydrides from aldehydes or alcohols via oxidative cross-coupling
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A novel type of metal-free oxidative cross-coupling for the synthesis of symmetrical and mixed anhydrides from aldehydes or benzylic alcohols has been developed. The aldehydes or alcohols were converted in situ into their corresponding acyl chlorides, which were then reacted with an array of carboxylic acids. The methodology has a general applicability, and was successfully employed to prepare either aromatic or aliphatic symmetrical anhydrides and mixed anhydrides, which are very unstable compounds.
- Gaspa, Silvia,Amura, Ida,Porcheddu, Andrea,De Luca, Lidia
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supporting information
p. 931 - 939
(2017/02/10)
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- A General Cp*CoIII-Catalyzed Intramolecular C?H Activation Approach for the Efficient Total Syntheses of Aromathecin, Protoberberine, and Tylophora Alkaloids
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Herein, we report a Cp*CoIII-catalyzed C?H activation approach as the key step to create highly valuable isoquinolones and pyridones as building blocks that can readily be applied in the total syntheses of a variety of aromathecin, protoberberine, and tylophora alkaloids. This particular C?H activation/annulation reaction was achieved with several terminal as well as internal alkyne coupling partners delivering a broad scope with excellent functional group tolerance. The synthetic applicability of this protocol reported herein was demonstrated in the total syntheses of two Topo-I-Inhibitors and two 8-oxyprotoberberine cores that can be further elaborated into the tetrahydroprotoberberine and the protoberberine alkaloid core. Moreover these building blocks were also transformed to six different tylophora alkaloids in expedient fashion.
- Lerchen, Andreas,Knecht, Tobias,Koy, Maximilian,Daniliuc, Constantin G.,Glorius, Frank
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supporting information
p. 12149 - 12152
(2017/09/13)
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- Continuous preparation technology of m-methyl benzoyl chloride
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The invention relates to a continuous preparation technology of m-methyl benzoyl chloride, and belongs to the technical field of fine chemical engineering. The continuous preparation technology comprises the steps of adding m-methyl benzoic acid, thionyl chloride and an organic solvent in a reaction kettle for reaction under a condition that a phase transfer catalyst exists, and obtaining reaction liquid; then adding the reaction liquid in a rectifying tower for carrying out normal-pressure rectifying so as to recycle the thionyl chloride and the organic solvent in the reaction liquid, and obtaining a m-methyl benzoyl chloride crude product; adding the m-methyl benzoyl chloride crude product in a film evaporator to carry out pressure-reduction distillation, and obtaining the m-methyl benzoyl chloride. According to the continuous preparation technology disclosed by the invention, the problems existing in a batch method/technology that the product quality is unstable, the automation degree of a device is low, and the labor intensity is large are solved; the continuous preparation technology has the characteristics that the technological route is concise, the production period is short, and the product yield is high; a side reaction can be prevented from being generated while the production capacity is increased.
- -
-
Paragraph 0026; 0027; 0028; 0029; 0030
(2016/10/07)
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- From Lead to Drug Candidate: Optimization of 3-(Phenylethynyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine Derivatives as Agents for the Treatment of Triple Negative Breast Cancer
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Herein we report the sophisticated process of structural optimization toward a previously disclosed Src inhibitor, compound 1, which showed high potency in the treatment of triple negative breast cancer (TNBC) both in vitro and in vivo but had considerable toxicity. A series of 3-(phenylethynyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine derivatives were synthesized. In vitro cell-based phenotypic screening together with in vivo assays and structure-activity relationship (SAR) studies finally led to the discovery of N-(3-((4-amino-1-(trans-4-hydroxycyclohexyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)ethynyl)-4-methylphenyl)-4-methyl-3-(trifluoromethyl)benzamide (13an). 13an is a multikinase inhibitor, which potently inhibited Src (IC50 = 0.003 μM), KDR (IC50 = 0.032 μM), and several kinases involved in the MAPK signal transduction. This compound showed potent anti-TNBC activities both in vitro and in vivo, and good pharmacokinetic properties and low toxicity. Mechanisms of action of anti-TNBC were also investigated. Collectively, the data obtained in this study indicate that 13an could be a promising drug candidate for the treatment of TNBC and hence merits further studies.
- Zhang, Chun-Hui,Chen, Kai,Jiao, Yan,Li, Lin-Li,Li, Ya-Ping,Zhang, Rong-Jie,Zheng, Ming-Wu,Zhong, Lei,Huang, Shen-Zhen,Song, Chun-Li,Lin, Wan-Ting,Yang, Jiao,Xiang, Rong,Peng, Bing,Han, Jun-Hong,Lu, Guang-Wen,Wei, Yu-Quan,Yang, Sheng-Yong
-
supporting information
p. 9788 - 9805
(2016/11/19)
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- Expedient Iron-Catalyzed C-H Allylation/Alkylation by Triazole Assistance with Ample Scope
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Triazole assistance set the stage for a unified strategy for the iron-catalyzed C-H allylation of arenes, heteroarenes, and alkenes with ample scope. The versatile catalyst also proved competent for site-selective methylation, benzylation, and alkylation with challenging primary and secondary halides. Triazole-assisted C-H activation proceeded chemo-, site-, and diastereo-selectively, and the modular TAM directing group was readily removed in a traceless fashion under exceedingly mild reaction conditions. One for all: A unified strategy for iron-catalyzed C-H allylation and alkylation was developed by the use of a triazole directing group that could be cleaved under exceedingly mild conditions.
- Cera, Gianpiero,Haven, Tobias,Ackermann, Lutz
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supporting information
p. 1484 - 1488
(2016/02/12)
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- Copper-Catalyzed Divergent Trifluoromethylation/Cyclization of Unactivated Alkenes
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Most of the precedent copper-catalyzed trifluoromethylation reactions of unactivated alkenes concern terminal alkenes, and these processes are terminated in elimination, or nucleophilic addition, or semipinacol rearrangement, or C-H bond functionalization steps. In this study, we develop a trifluoromethylation method for both unactivated terminal and internal alkenes to enable divergent late-stage radical cyclization and achieve high molecular complexity. These cyclizations are well consistent with Baldwin's rule. Furthermore, a kinetic isotope effect (KIE) study and control reactions were conducted, and a plausible mechanism is proposed.
- Zheng, Jing,Deng, Ziyang,Zhang, Yan,Cui, Sunliang
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supporting information
p. 746 - 751
(2016/03/09)
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- Design, synthesis and antibacterial activity of isatin derivatives as FtsZ inhibitors
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Seven isatin derivatives have been designed, and their chemical structures were characterized by single crystal X-ray diffraction studies, 1H NMR, MS, and elemental analysis. Structural stabilization followed by intramolecular as well as intermolecular H-bonds makes these molecules as perfect examples in molecular recognition with self-complementary donor and acceptor units within a single molecule. These compounds were evaluated for antimicrobial activities. Docking simulations have been performed to position compounds into the FtsZ active site to determine their probable binding models. All of the compounds exhibited better antibacterial activities. Interestingly, compound 5c and 5d exhibited better antibacterial activities with IC50 values of 0.03 and 0.05 μmol/mL against Staphylococcus aureus, respectively. Compound 5g displays antibacterial activity with IC50 values of 0.672 and 0.830 μmol/mL against Escherichia coli and Pseudomonas aeruginosa, respectively.
- Lian, Zhi-Min,Sun, Juan,Zhu, Hai-Liang
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-
- Diastereoselective [3+2] Annulation of Aromatic/Vinylic Amides with Bicyclic Alkenes through Cobalt-Catalyzed C-H Activation and Intramolecular Nucleophilic Addition
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A highly diastereoselective method for the synthesis of dihydroepoxybenzofluorenone derivatives from aromatic/vinylic amides and bicyclic alkenes is described. This new transformation proceeds through cobalt-catalyzed C-H activation and intramolecular nucleophilic addition to the amide functional group. Transition-metal-catalyzed C-H activation reactions of secondary amides with alkenes usually lead to [4+2] or [4+1] annulation; to the best of our knowledge, this is the first time that a [3+2] cycloaddition is described in this context. The reaction proceeds under mild conditions and tolerates a wide range of functional groups. Mechanistic studies imply that the C-H bond cleavage may be the rate-limiting step. [3+2] instead of [4+2] or [4+1]: The diastereoselective [3+2] annulation of secondary amides with alkenes proceeds by cobalt-catalyzed C-H activation and intramolecular nucleophilic addition to the amide functional group under mild conditions. Mechanistic studies suggest that the C-H bond cleavage is the rate-limiting step.
- Gandeepan, Parthasarathy,Rajamalli, Pachaiyappan,Cheng, Chien-Hong
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supporting information
p. 4308 - 4311
(2016/04/01)
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- Transition-Metal-Free Synthesis of N-Aryl Hydroxamic Acids via Insertion of Arynes
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An efficient and transition-metal-free N-arylation of amides via the insertion of arynes into the N-H bonds in the N-alkoxy amides is described. A variety of the reactive functional groups including the reactive aldehyde carbonyl group, furan ring, carbon-carbon double bonds, and free N-H bond of indole are found to be compatible with this process. In particular, the protocol is applicable in the synthesis of structurally diverse N-aryl hydroxamates and hydroxamic acids derived from N-protecting amino acids and peptides. In the presence of multiple amide N-H bonds, the N-arylation reaction can proceed selectively in the N-H bonds of terminal N-OBn amides giving rise to the desired N-aryl hydroxamates.
- Zhang, Lanlan,Geng, Yu,Jin, Zhong
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p. 3542 - 3552
(2016/05/24)
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- Ligand-Promoted Rh(III)-Catalyzed Coupling of Aryl C-H Bonds with Arylboron Reagents
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Rhodium(III)-catalyzed C-H arylation of arenes with phenylboronic acid pinacol esters has been achieved using a readily removable N-pentafluorophenylbenzamide directing group for the first time. The use of a bidentate phosphine ligand (Binap) significantly increased the yield of the cross-coupling of C-H bonds with organoboron reagents.
- Wang, Huai-Wei,Cui, Pei-Pei,Lu, Yi,Sun, Wei-Yin,Yu, Jin-Quan
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p. 3416 - 3422
(2016/05/19)
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- Design, synthesis and fungicidal activity of N-substituted benzoyl-1,2,3,4-tetrahydroquinolyl-1-carboxamide
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To find a new lead compound with high biological activity, a series of N-substituted benzoyl-1,2,3,4-tetrahydroquinolyl-1-carboxamide were designed using linking active substructures method. The target compounds were synthesized from substituted benzoic acid by four steps and their structures were confirmed by 1H NMR, IR spectrum and elemental analysis. The in vitro bioassay results indicated that some target compounds exhibited excellent fungicidal activities, and the position of the substituents played an important role in fungicidal activities. Especially, compound 5n, exhibited better fungicidal activities than the commercial fungicide flutolanil against two tested fungi Valsa Mali and Sclerotinia sclerotiorum, with EC50 values of 3.44 and 2.63 mg/L, respectively. And it also displayed good in vivo fungicidal activity against S. sclerotiorum with the EC50 value of 29.52 mg/L.
- Lei, Peng,Xu, Yan,Du, Juan,Yang, Xin-Ling,Yuan, Hui-Zhu,Xu, Gao-Fei,Ling, Yun
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supporting information
p. 2544 - 2546
(2016/07/07)
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- Synthesis and biological evaluation of 1-(2-aminophenyl)-3-arylurea derivatives as potential EphA2 and HDAC dual inhibitors
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A series of 1-(2-aminophenyl)-3-arylurea novel derivatives were synthesized and evaluated against Ephrin type-A receptor 2 (EphA2) and histone deacetylases (HDACs) kinase. Most of the compounds exhibited inhibitory activity against EphA2 and HDAC. The antiproliferative activities were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) (thiazolyl blue, tetrazolium blue) against the human cancer cell lines HCT116, K562 and MCF7. Compounds 5a and b showed the most potent inhibitory activity against EphA2 and HDAC. However, compound 5b exhibited higher potency against HCT116 (IC50=5.29 μM) and MCF7 (IC50=7.42 μM). 1-(2-Aminophenyl)-3-arylurea analogues may serve as new EphA2-HDAC dual inhibitors.
- Zhu, Yong,Ran, Ting,Chen, Xin,Niu, Jiaqi,Zhao, Shuang,Lu, Tao,Tang, Weifang
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p. 1136 - 1141
(2016/08/11)
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- Rh-Catalyzed annulations of: N -methoxybenzamides with ketenimines: Synthesis of 3-aminoisoindolinones and 3-diarylmethyleneisoindolinones with strong aggregation induced emission properties
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Rhodium-catalyzed C-H activation/annulation reactions of ketenimines with N-methoxybenzamides furnished 3-aminoisoindolin-1-ones and 3-(diarylmethylene)isoindolin-1-ones. The synthesized 3-(diarylmethylene)isoindolin-1-ones exhibited aggregation induced emissions in aqueous tetrahydrofuran solution and strong green-yellow emissions in solids.
- Zhou, Xiaorong,Peng, Zhixing,Zhao, Hongyang,Zhang, Zhiyin,Lu, Ping,Wang, Yanguang
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supporting information
p. 10676 - 10679
(2016/09/02)
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- Synthesis and Quantitative Structure-activity Relationships Study for Arylpropenamide Derivatives as Inhibitors of Hepatitis B Virus Replication
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A series of new arylpropenamide derivatives containing different aryl groups were synthesized, characterized, and evaluated for their anti-hepatitis B virus (HBV) activities. A new high accuracy QSAR model of arylpropenamide was constructed based on a more completely activities data and calculation parameter. The 2D-QSAR equations, by using DFT and multiple linear regression analysis methods, revealed that higher value of thermal energy (TE) and lower entropy (S?) increase the anti-HBV activities of the arylpropenamide molecules. Predictive 3D-QSAR models were established by SYBYL multifit molecular alignment rule. The optimum models were all statistically significant with cross-validated and conventional coefficients, indicating that they were reliable enough for activity prediction.
- Min, Ma,Xingjun, Jiang,Xueding, Wang,Hao, Zou,Weiqing, Yang,Yuanyuan, Zhang,Changrong, Peng,Zicheng, Li,Jing, Yang,Quan, Du,Menglin, Ma
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p. 451 - 459
(2016/10/19)
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- Palladium-catalyzed electrophilic C–H fluorination of arenes using oxazoline as a removable directing group
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Dimethyloxazoline was rationally designed to act as a removable ortho-directing group (DG) for the palladium-catalyzed C–H electrophilic fluorination of arenes. Using NFSI as the fluorinating agent, and Pd(II), Ag(I) catalytic system, electrophilic C(sp2–H) ortho-fluorination took place on a variety of aryl substrates to afford the corresponding mono- and di-fluorinated products.
- Gutierrez, David A.,Lee, Wan-Chen Cindy,Shen, Yuning,Li, Jie Jack
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supporting information
p. 5372 - 5376
(2016/11/11)
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- 4-Amino-2,1,3-benzothiadiazole as a Removable Bidentate Directing Group for the Pd(II)-Catalyzed Arylation/Oxygenation of sp2/sp3 β-C-H Bonds of Carboxamides
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In this paper, we report 4-amino-2,1,3-benzothiadiazole (ABTD) as a new bidentate directing group for the Pd(II)-catalyzed sp2/sp3 C-H activation/functionalization of various aliphatic/alicyclic/aromatic carboxamide systems. The Pd(II)-catalyzed, ABTD-directed sp3 C-H arylation/acetoxylation of aliphatic- and alicyclic carboxamides afforded the corresponding β-C-H arylated/acetoxylated carboxamides. The Pd(II)-catalyzed, ABTD-directed sp3 C-H arylation of cyclobutanecarboxamide with different aryl iodides afforded the corresponding bis β-C-H arylated cyclobutanecarboxamides having all-cis stereochemistry with a high degree of stereocontrol. The Pd(II)-catalyzed, ABTD-directed arylation/benzylation/acetoxylation/alkoxylation of ortho C(sp2)-H bonds of various benzamides afforded the corresponding ortho C-H arylated/benzylated/oxygenated benzamides. The observed regio- and stereoselectivity in the Pd(II)-catalyzed, ABTD-directed arylation/benzylation of aliphatic/alicyclic carboxamides and benzamides were ascertained from the X-ray structures of representative compounds 5g (bis-β-C(sp3)-H arylated cyclobutanecarboxamide) and 7f (ortho C(sp2)-H arylated benzamide). A brief description on the efficiency, scope, and limitations of bidentate directing group ABTD is reported.
- Reddy, Chennakesava,Bisht, Narendra,Parella, Ramarao,Babu, Srinivasarao Arulananda
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p. 12143 - 12168
(2016/12/23)
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- Regiocontrolled Coupling of Aromatic and Vinylic Amides with α-Allenols to Form γ-Lactams via Rhodium(III)-Catalyzed C-H Activation
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A mild, regiocontrolled coupling of aromatic and vinylic amides with α-allenols to form γ-lactams via rhodium(III)-catalyzed C-H activation has been demonstrated. This [4 + 1] annulation reaction provides an efficient method for the synthesis of isoindolinones and 1,5-dihydro-pyrrol-2-ones bearing a tetrasubstituted carbon atom α to the nitrogen atom with good functional group tolerance. The hydroxyl group in the allene substrate is essential in controlling the chemo- and regioselectivity of the reaction probably by coordination interaction with the rhodium catalyst.
- Zhou, Zhi,Liu, Guixia,Lu, Xiyan
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supporting information
p. 5668 - 5671
(2016/11/17)
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- Rhodium(iii)-catalyzed C-H/C-C activation sequence: Vinylcyclopropanes as versatile synthons in direct C-H allylation reactions
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Succession of C-H activation and C-C activation was achieved by using a single rhodium(iii) catalyst. Vinylcyclopropanes were used as versatile coupling partners. Mechanistic studies suggest that the olefin insertion step is rate-determining and a facile β-carbon elimination is involved, which represents a novel ring opening mode of vinylcyclopropanes. This journal is
- Wu, Jia-Qiang,Qiu, Zhi-Ping,Zhang, Shang-Shi,Liu, Jing-Gong,Lao, Ye-Xing,Gu, Lian-Quan,Huang, Zhi-Shu,Li, Juan,Wang, Honggen
-
supporting information
p. 77 - 80
(2015/01/09)
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- Design and synthesis of novel 3,5-substituted indolin-2-one derivatives
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In this paper, twelve novel 3,5-substituted indolin-2-one derivatives were designed and synthesized based on indolin-2-one. The structures of the new compounds have been confirmed by 1 H NMR, HR-MS and IR spectra analysis. This study provides a new method for development of indolin-2-one derivatives.
- Zhang, Yi-Ying,Liu, Yuan,Wang, Yu-Liang
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p. 491 - 495
(2015/02/05)
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- Copper/silver-mediated direct ortho-ethynylation of unactivated (hetero)aryl C-H bonds with terminal alkyne
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A copper/silver-mediated oxidative ortho-ethynylation of unactivated aryl C-H bonds with terminal alkyne has been developed.The reaction uses the removable PIP directing group and features broad substrate scope, high functional-group tolerance, and compatibility with a wide range of heterocycles, providing an efficient synthesis of aryl alkynes. This procedure highlights the potential of copper catalysts to promote unique, synthetically enabling C-H functionalization reactions that lie outside of the current scope of precious metal catalysis.
- Liu, Yue-Jin,Liu, Yan-Hua,Yin, Xue-Song,Gu, Wen-Jia,Shi, Bing-Feng
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supporting information
p. 205 - 209
(2015/02/19)
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- Cu(II)-catalyzed coupling of aromatic C-H bonds with malonates
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A new Cu(II)-catalyzed oxidative coupling of arenes with malonates has been developed using an amide-oxazoline directing group. The reaction proceeds via C(sp2)-H activation and malonate coupling, followed by intramolecular oxidative N-C bond formation. A variety of arenes bearing different substituents are shown to be compatible with this reaction.
- Wang, Hong-Li,Shang, Ming,Sun, Shang-Zheng,Zhou, Zeng-Le,Laforteza, Brian N.,Dai, Hui-Xiong,Yu, Jin-Quan
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supporting information
p. 1228 - 1231
(2015/03/14)
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- Nickel-catalyzed directed sulfenylation of sp2 and sp3 C-H bonds
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Directed sulfenylation of both sp2 and sp3 C-H bonds was achieved through nickel catalyzed directed C-S bond formation, giving the desired product in good to excellent yield (up to 90%). Other metal cations, including Cu, Fe, Pd, Rh, Ru and Co, gave almost no reaction under identical conditions, which highlighted the unique reactivity of this Ni system.
- Ye, Xiaohan,Petersen, Jeffrey L.,Shi, Xiaodong
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supporting information
p. 7863 - 7866
(2015/05/13)
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- Carboxylate Assisted Ni-Catalyzed C-H Bond Allylation of Benzamides
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A one-step synthetic method was developed for allylation of benzamides using Ni(COD)2/RCO2H and [Ni(μ-H2O)(OOCCMe3)2(HOOCCMe3)2]2 (A′) catalytic system. Efficient, well-defined, air and moisture-stable Ni-pivalate complex was isolated and employed in catalytic allylation. The influence of solvent on product selectivity was also investigated. Nickel-back: A one-step synthetic method was developed for the allylation of benzamides using in situ formed nickel carboxylate Ni(COD)2/RCO2H catalyst (see scheme). The air and moisture stable Ni-pivalate complex was isolated and employed in catalytic allylation. The influence of solvent on product selectivity is discussed.
- Barsu, Nagaraju,Kalsi, Deepti,Sundararaju, Basker
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supporting information
p. 9364 - 9368
(2015/06/30)
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- Copper-catalyzed direct acyloxylation of C(sp2)-H bonds with Benzoic acids
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A copper-catalyzed acyloxylation of C(sp2)-H bond with sterically bulky benzoic acids was achieved. This protocol is compatible with a broad range of functional groups and could proceed in gram scale, providing an efficient and practical protoc
- Zhao, Sheng,Chen, Fa-Jie,Liu, Bin,Shi, Bing-Feng
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p. 1302 - 1309
(2015/03/30)
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- Synthesis and biological evaluation of acetylenic chalcones as novel anti-inflammatory agents
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37 acetylenic chalcones were designed, synthesized by the Pd/Cu catalyzed Sonogashira coupling reaction, and evaluated for anti-inflammatory activities. A majority of these compounds showed remarkable inhibitions of the expression of inflammatory cytokine
- Zhao, Chengguang,Feng, Jianpeng,Zuo, Mingming,Zhang, Ying,Zhao, Jianfeng,Xu, Shanmei,Zheng, Suqing,Zhang, Yali,Tang, Qinqin,Lu, Zhongqiu,Liang, Guang,Zhou, Jianmin
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p. 567 - 572
(2015/08/18)
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- A Mild and Regioselective Route to Functionalized Quinazolines
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A Rh-catalyzed ortho-amidation cyclocondensation sequence gave a range of 4-aminoquinazolines in high yield. The method features a remarkably mild C(sp2)-H activation step and can be exploited to rapidly access compounds with established biological activity.
- Maiden, Tracy M. M.,Swanson, Stephen,Procopiou, Panayiotis A.,Harrity, Joseph P. A.
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supporting information
p. 14342 - 14346
(2015/10/05)
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- Benzimidazole or diamide from a reaction of diamines and carboxylic acids or acid chlorides: Crystal structures and theoretical studies
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A reaction of an acid chloride with a diamine yielded a diamide. m-Toluic acid was chlorinated to m-toluoyl chloride and subsequently reacted with 4-methyl-o-phenylenediamine in pyridine to obtain 3-methyl-N-[2-(3-methylbenzamido) phenylbenzamide (I). 2-(
- Odame, Felix,Hosten, Eric,Betz, Richard,Lobb, Kevin,Tshentu, Zenixole R.
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p. 986 - 994
(2016/01/20)
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- Metal-Free Direct Oxidation of Aldehydes to Esters Using TCCA
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Aromatic and aliphatic aldehydes are simply converted into esters by an efficient oxidative esterification carried out under mild conditions. The aldehydes are converted in situ into their corresponding acyl chlorides, which are then reacted with primary and secondary aliphatic, benzylic, allylic, and propargylic alcohols and phenols. A variety of esters are obtained in high yields.
- Gaspa, Silvia,Porcheddu, Andrea,De Luca, Lidia
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supporting information
p. 3666 - 3669
(2015/08/18)
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- Synthesis and antibacterial activity of novel levofloxacin analogues
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To search for new fluoroquinolones with better biological activities, twenty-six levofloxacin analogues were designed, synthesized and evaluated for antimicrobial activity against Gram-positive and Gram-negative bacterias. The results indicated that most compounds tested in this study exhibited comparable or better antimicrobial activity than levofloxacin as reference drug. Among these compounds, ZY6a was the most active compound against Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa, its activity was found to be 2 to 16 times better than levofloxacin.
- Zhang, Tong-Xin,Zhang, Wei-Xi,Zhu, Hua-Jun,Liang, Long,Cheng, Zhi-Peng,Luo, Mei-Ming
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p. 2344 - 2350
(2014/06/09)
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- Synthesis and evaluation of some substituted heterocyclic fluconazole analogues as antifungal agents
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A new series of fluconazole analogues of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4- difluoro-phenyl)-3-4-(substituted-heterocyclic ring-1H-1,2,3- triazol-1-yl)-2-propanols (1-10) were designed, synthesized and evaluated as antifungal agents. Preliminary antifungal tests showed that most of the title compounds exhibited moderate activity with broad spectrum against eight human pathogenic fungi in vitro, compounds 1 and 6 had the best antifungal activity against Candida albicans with the value of MIC80 = 0.5 μg/mL respectively.
- Wang, Shudong,Zhang, Lei,Jin, Yongsheng,Tang, Jin Hao,Su, Hua,Yu, Shichong,Ren, Haixiang
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p. 2362 - 2364
(2014/06/09)
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- Design, synthesis, molecular docking studies and in vitro screening of ethyl 4-(3-benzoylthioureido) benzoates as urease inhibitors
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Thioureas are exceptionally versatile building blocks towards the synthesis of wide variety of heterocyclic systems, which also possess extensive range of pharmacological activities. The substituted benzoic acids were converted into corresponding acid chlorides, these acid chlorides were then treated with potassium thiocyanate in acetone and then the reaction mixture was refluxed for 1-2 h afford ethyl 4-(3-benzoylthioureido)benzoates thioureas in good yields. All the newly synthesized compounds were evaluated for their urease inhibitory activities and were found to be potent inhibitors of urease enzyme. Compounds 1f and 1g were identified as the most potent urease inhibitors (IC50 0.21 and 0.13 μM, respectively), and was 100-fold more potent than the standard inhibitors. Further molecular docking studies were carried out using the crystal structure of urease to find out the binding mode of the inhibitors with the enzyme.
- Saeed, Aamer,Khan, Muhammad Siraj,Rafique, Hummera,Shahid, Mohammad,Iqbal, Jamshed
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- Synthesis and evaluation of novel azoles as potent antifungal agents
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Using a rational approach to the design of antifungal agents, a series of azole agents with 1,3,4-oxadiazole side chains were designed and synthesized. The results of preliminary in vitro antifungal tests with eight human pathogenic compounds showed that all of the title compounds exhibited excellent activities against all of the tested fungi except Aspergillus fumigatus. Compounds 11e and 11f were found to be the most effective, with a minimum inhibitory concentration of 0.0039 μg/mL, followed by voriconazole, which has a MIC of 0.0625 μg/mL. The 1,3,4-oxadiazole side chain is not the major contributor but plays a role in eliciting the observed antifungal activity.
- Li, Liangjing,Ding, Hao,Wang, Baogang,Yu, Shichong,Zou, Yan,Chai, Xiaoyun,Wu, Qiuye
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supporting information
p. 192 - 194
(2014/01/17)
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- Rhodium-catalyzed C-H alkynylation of arenes at room temperature
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The rhodium(III)-catalyzed ortho C-H alkynylation of non-electronically activated arenes is disclosed. This process features a straightforward and highly effective protocol for the synthesis of functionalized alkynes and represents the first example of merging a hypervalent iodine reagent with rhodium(III) catalysis. Notably, this reaction proceeds at room temperature, tolerates a variety of functional groups, and more importantly, exhibits high selectivity for monoalkynylation. Hot rhod: A rhodium-catalyzed, electronically reversed Sonogashira reaction between unbiased arenes and the hypervalent iodine reagent 1 proceeds through C-H activation. This reaction displays excellent functional-group tolerance and high efficiency, and thus opens a new synthetic pathway to access functionalized alkynes. Cp=C5Me5, DCE=1,2-dichloroethane, Piv=pivaloyl, TIPS=triisopropylsilyl.
- Feng, Chao,Loh, Teck-Peng
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supporting information
p. 2722 - 2726
(2014/03/21)
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- Palladium(II)-catalyzed ortho-C-H arylation/alkylation of N-benzoyl α-amino ester derivatives
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The palladium-catalyzed arylation/alkylation of ortho-C-H bonds in N-benzoyl α-amino ester derivatives is described. In such a system both the NH-amido and the CO2R groups in the α-amino ester moieties play a role in successful C-H activation/C-C bond formation using iodoaryl coupling partners. A wide variety of functional groups and electron-rich/ deficient iodoarenes are tolerated. The yields obtained range from 20 to 95 %. C-H activation: The transformation of N-benzoyl amino acid ester derivatives (Gly, Asp) has been studied, in which the ortho-C-H activation/C-C bond formation was achieved by using the synergistic system Pd(OAc)2/AgOAc and halide compounds as coupling partners in t-Amyl-OH under air (see scheme).
- Misal Castro, Luis C.,Chatani, Naoto
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supporting information
p. 4548 - 4553
(2014/05/06)
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- Copper-mediated hydroxylation of arenes and heteroarenes directed by a removable bidentate auxiliary
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A copper-mediated C-H hydroxylation of arenes and heteroarenes using our newly developed PIP directing group has been developed. This procedure is scalable and compatible with a wide range of functional groups and heteroarenes, providing an operationally simple protocol for the synthesis of o-hydroxybenzamides. The hydroxylation of nicotinamides gave 4-oxo-1,4-dihydropyridine-3-carboxamides selectively. Preliminary mechanistic studies implicate that a basic ligand-enabled, irreversible, rate-determining CMD step is most likely involved in this process.
- Li, Xin,Liu, Yan-Hua,Gu, Wen-Jia,Li, Bo,Chen, Fa-Jie,Shi, Bing-Feng
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supporting information
p. 3904 - 3907
(2014/08/18)
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- Ni(II)-catalyzed oxidative coupling between C(sp2)-H in benzamides and C(sp3)-H in toluene derivatives
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Oxidative coupling between C(sp2)-H bonds and C(sp3)-H bonds is achieved by the Ni(II)-catalyzed reaction of benzamides containing an 8-aminoquinoline moiety as the directing group with toluene derivatives in the presence of heptafluoroisopropyl iodide as the oxidant. The method has a broad scope and shows high functional group compatibility. Toluene derivatives can be used as the coupling partner in an unreactive solvent.
- Aihara, Yoshinori,Tobisu, Mamoru,Fukumoto, Yoshiya,Chatani, Naoto
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supporting information
p. 15509 - 15512
(2014/12/11)
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- Metal-free iodine(III)-promoted synthesis of isoquinolones
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A metal-free oxidative cycloaddition reaction of substituted benzamides and alkynes has been developed for the synthesis of isoquinolones by using bis(trifluoracetoxy)iodobenzene (PIFA) and trifluoroacetic acid (TFA). Under mild conditions, a wide variety of isoquinolones were conveniently prepared via oxidative annulation of simple N-methoxybenzamide and diarylacetylene or aryl/alkyl acetylene derivatives in yields up to 87%.
- Chen, Zhi-Wei,Zhu, Yi-Zhou,Ou, Jin-Wang,Wang, Ya-Ping,Zheng, Jian-Yu
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p. 10988 - 10998
(2015/01/08)
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- Mild rhodium(III)-catalyzed C-H allylation with 4-vinyl-1,3-dioxolan-2-ones: Direct and stereoselective synthesis of (E)-allylic alcohols
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A rhodium(III)-catalyzed C-H direct allylation reaction with 4-vinyl-1,3-dioxolan-2-ones has been developed. The reaction provides a facile and stereoselective access to substituted-(E)-allylic alcohols under mild and redox-neutral reaction conditions. Olefinic C-H activation is applicable, giving multifunctionalized skipped dienes in good yields. Minimal double-bond migration was observed.
- Zhang, Shang-Shi,Wu, Jia-Qiang,Lao, Ye-Xing,Liu, Xu-Ge,Liu, Yao,Lv, Wen-Xin,Tan, Dong-Hang,Zeng, Yao-Fu,Wang, Honggen
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supporting information
p. 6412 - 6415
(2015/01/09)
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- Copper-catalyzed phosphorylation of sp2 C-H bonds
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The phosphorylation of the ortho C-H bonds in benzamides containing an 8-aminoquinoline moiety as a bidentate directing group with H-phosphonates using copper as a catalyst under mild temperature conditions is described. This method shows high functional group compatibility and selectively gives mono-substituted products. This journal is
- Wang, Shan,Guo, Rui,Wang, Gao,Chen, Shan-Yong,Yu, Xiao-Qi
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supporting information
p. 12718 - 12721
(2015/05/20)
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